title: Micelle-based activatable probe for in vivo near-infrared optical imaging of cancer biomolecules.
abstract: Near-infrared (NIR: 800-1000 nm) fluorescent probes, which activate their fluorescence following interaction with functional biomolecules, are desirable for noninvasive and sensitive tumor diagnosis due to minimal tissue interference. Focusing on bioavailability and applicability, we developed a probe with a self-assembling polymer micelle, a lactosome, encapsulating various quantities of NIR dye (IC7-1). We also conjugated anti-HER2 single chain antibodies to the lactosome surface and examined the probe's capacity to detect HER2 in cells and in vivo. Micelles encapsulating 20mol% IC7-1 (hIC7L) showed 30-fold higher fluorescence (λem: 858 nm) after micelle denaturation compared to aqueous buffer. Furthermore, antibody modification allowed specific activation of the probe (HER2-hIC7L) following internalization by HER2-positive cells, with the probe concentrating in lysosomes. HER2-hIC7L intravenously administered to mice clearly and specifically visualized HER2-positive tumors by in vivo optical imaging. These results indicate that HER2-hIC7L is a potential activatable NIR probe for sensitive tumor diagnosis.
  
  
  BACKGROUND
  Near-infrared probes that activate their fluorescence following interaction with specific biomolecules are desirable for noninvasive and sensitive tumor detection due to minimal tissue interference. This team of authors developed a probe termed hIC7L and demonstrate its potential in HER2 tumor diagnosis.
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Temma
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Hara
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Makino
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamahara
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan.
authors.forename: Ei-Ichi
authors.initials: E
authors.lastname: Ozeki
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. Electronic address: hsaji@pharm.kyoto-u.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D051379:Mice; D008823:Micelles; D008856:Microscopy, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D019265:Spectroscopy, Near-Infrared
chemical_list: D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D008823:Micelles; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Activatable probe; Lactosome; Molecular imaging; Near-infrared fluorescence imaging; Polymeric micelle